Versatile Chiral Building Blocks by Catalytic C-H and C-C Activation

通过催化 C-H 和 C-C 活化形成多功能手性结构单元

• 批准号: 1797595
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1797595
• 关键词: Versatile; Chiral; Building; Blocks; Catalytic

Axially chiral biaryl compounds are of high importance as they are widely used as auxiliary ligands in asymmetric reactions giving high enantioselectivities and form a part of many biologically active natural products. Although axially chiral biaryl compounds are an attractive synthetic target, they are difficult to make. One of the main limitations to existing methods is a limited substrate scope, thus a more general method for the synthesis of axially chiral biaryls is needed. To develop such a method, two approaches that involve catalytic C-C and C-H activation will be explored in this project. In particular, a range of functionalised biaryls will be obtained by C-C functionalisation of strained C-C bonds in biphenylenes (Fig. 1, Scheme A) and ortho C-H bonds in biphenyls (Fig. 2, Scheme B). To develop the C-C functionalisation approach, a range of palladium, nickel, rhodium and iridium metal precursors with a variety of ligands will be initially tested in a model reaction to identify the best catalytic system. The scope of this approach will then be explored by trialling functionalisation of the biphenylenes with a range of boranes, diboranes and silaboranes. Boryl or silyl substituted biaryls are of particular interest because they are amenable to subsequent functionalisation, thus they have the potential to give access to a wide substrate scope. In addition, biphenylenes with a variety of R-substituents will be tested in the reaction to see what effect electronics and sterics have on the ring opening. In the second approach C-H activation, a directing group will be used to add functionality in the ortho position using a transition metal catalyst (Fig 1. Scheme B). The functional groups to be explored include boryl, silyl, alkynyl, and amino, similarly because they are amenable to subsequent functionalisation. Chirality induction in both approaches will be achieved by the use of chiral metal catalysts and achiral metal catalysts in the presence of chiral additives.

轴向手性联芳基化合物是一类重要的手性化合物，它们在不对称反应中被广泛用作辅助配体，具有很高的对映选择性，是许多具有生物活性的天然产物的一部分。虽然轴向手性联芳基化合物是一个有吸引力的合成目标，但它们很难制备。现有方法的主要局限之一是底物范围有限，因此需要一种更通用的方法来合成轴向手性联芳基化合物。为了开发这样的方法，本项目将探索两种涉及催化C-C和C-H活化的方法。特别地，一系列官能化联芳基将通过联苯中的应变C-C键（图1，方案A）和联苯中的邻位C-H键（图2，方案B）的C-C官能化来获得。为了开发C-C官能化方法，将在模型反应中初步测试一系列具有各种配体的钯、镍、铑和铱金属前体，以确定最佳催化体系。这种方法的范围，然后将探讨通过试用功能化的联苯与一系列的硼烷，乙硼烷和硅硼烷。硼基或甲硅烷基取代的联芳基特别令人感兴趣，因为它们易于随后官能化，因此它们具有获得广泛底物范围的潜力。此外，具有各种R-取代基的联苯将在反应中进行测试，以了解电子和立体对开环的影响。在第二种方法C-H活化中，使用过渡金属催化剂将导向基团用于在邻位添加官能度（图1）。方案B）。待探索的官能团包括硼基、甲硅烷基、炔基和氨基，类似地，因为它们适合于随后的官能化。两种方法中的手性诱导将通过使用手性金属催化剂和在手性添加剂存在下的非手性金属催化剂来实现。